ctDNA (MRD)-guided ACT (capecitabine±oxaliplatin) cuts 3-year recurrence in stage II MSS colon cancer

CIRCULATE (AIO KRK-0217/ABCSG; NCT04089631) used a tumor-informed NGS ctDNA assay post-op in stage II pMMR/MSS colon cancer: ctDNA+ patients were randomized to adjuvant chemotherapy (6 mo capecitabine or 3–6 mo CAPOX) vs observation, while ctDNA− patients were largely observed (blinded to ctDNA status). Among ctDNA+ patients, per-protocol chemo (n=26 randomized; some untreated excluded in PP) reduced 3-year recurrence from 62% to 19% (HR 0.21; p=0.009) and improved 3-year DFS from 38% to 77% (HR 0.28; p=0.022), but ITT did not reach significance (3-year DFS 61% vs 38%; HR 0.52; p=0.12); there was 1 treatment-related death. Versus “unselected” stage II where fluoropyrimidine ACT yields only small absolute benefit overall (and many low-risk patients do well with surgery alone), this trial suggests ctDNA identifies a small, very-high-risk slice that may actually derive meaningful DFS/TTR benefit from ACT—if the signal holds despite the tiny ctDNA+ sample and PP dependence.